The Ets family of transcription factors/protooncogenes have been implicated as factors involved in the regulation of genes important for hematopoietic function and viral activation. Our studies focus on elucidating the functional roles of two of the Ets genes, ets-1 and ets- 2, using transgenic technologies. Our approach has been to determine the normal expression patterns of the ets-1 and ets-2 genes, define the regulatory elements which govern the expression of these genes, and study in transgenic mice what phenotypic abnormalities result from the mis- expression or null mutations of these genes in vivo. Our results indicate that ets-1 and ets-2 are differentially expressed during mouse development and that multiple regulatory elements are required for the transcription of ets-1 in various tissues during development. Several transgenic studies are underway to mis-express the ets-1 and ets-2 genes in vivo. Multiple embryonic stem cell lines have been created which are hemizygous for the disruption of the ets-1 coding sequence. These cell lines are being injected to create null ets-1 transgenic animals.